Effect of white matter lesions on manual dexterity in healthy middle-aged persons

Objectives: We hypothesized that integrated motor-visual functions measured by manipulative manual dexterity are affected by white matter lesion (WML) burden as measured on cranial MRI across relevant brain regions in subjects at risk of preclinical occult vascular disease. Methods: A real-time cross-sectional study of healthy subjects aged 29 to 74 years with a family history of early-onset coronary artery disease (n 714; mean age, 51 ± 11 years; mean education, 14 ± 3 years; 42% male; 38% black) were identified from probands with coronary artery disease diagnosed before age 60 years. WMLs on 3-tesla brain MRI and Grooved Pegboard scores were measured. Results: WMLs were observed at all ages. Mean pegboard scores were 108 ± 18, similar to normal populations. In unadjusted analysis, WMLs and pegboard scores were significantly correlated by region (total WMLs, r 0.34, p 0.0001; frontal [r 0.34, p < 0.0001], insula [r 0.31, p < 0.0001], parietal [r 0.31, p < 0.0001], and temporal [r 0.17, p < 0.0001]). In multivariate analysis predicting (log) pegboard score adjusted for age, sex, race, education, regional or total volumes, and familial nonindependence, total WML volume (p 5.79E-05) and regional WML volumes (p < 0.01) retained statistical significance in all but the youngest age quartile (29-43 years). Conclusions: Greater WML volumes in different brain regions are associated with higher pegboard scores (worse performance) independent of age, sex, race, education, and total or regional volumes. This suggests that small vessel cerebrovascular disease may be present in healthy individuals in a preclinical state with measurable impact on complex integrative functions in individuals with excess risk of clinical vascular disease.